A high-performance extracellular field potential analyzer for iPSC-derived cardiomyocytes

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Electrophysiology

Background:

• Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are vital for cardiac research.
• Extracellular Field Potential (EFP) analysis offers electrocardiogram-like insights but is complex.
• Specialized expertise is often required, limiting broader laboratory use.

Purpose of the Study:

• To introduce EFP-Analyzer (EFPA), a semi-automated tool for analyzing iPSC-CM EFP traces.
• To simplify and standardize electrophysiological assessments in non-specialized labs.
• To validate EFPA's accuracy and reproducibility in analyzing cardiac electrophysiology.

Main Methods:

• Developed EFPA for semi-automated beat identification, averaging, and interval calculation from EFP traces.
• Analyzed 358 EFP traces from 22 patient-derived iPSC-CM lines (spontaneously beating and optically paced).
• Implemented stringent quality criteria and conducted inter-intra observer analysis for usability and replicability.

Main Results:

• EFPA demonstrated high inter-reader correlation (r: 0.93-1.00) for Field Potential Duration (FPD) measurements.
• Bland-Altman analysis showed narrow limits of agreement for FPD in both spontaneously beating and paced iPSC-CMs.
• EFPA accurately detected drug-induced (moxifloxacin) and mutation-induced (CACNA1C N639T) FPD prolongation.

Conclusions:

• EFPA provides a robust, user-friendly solution for analyzing iPSC-CM electrophysiology.
• The tool enhances data replicability and facilitates broader adoption of iPSC-CMs in research.
• EFPA aids in assessing drug safety and understanding genetic contributions to cardiac arrhythmias.